The invention comprises a method and apparatus for detecting neural injuries and predicting neurological outcome. In particular the invention is useful for detecting injuries to the immature cerebral white matter in preterm infants and for enabling rapid prediction of the development of subtle and severe lesions in the cerebral white matter of and neurological outcome for preterm infants.
Very premature infants have a markedly increased risk of neurological morbidity (Volpe, Prev. Med., 23: 638-645, 1994). A recent study using cranial ultrasonography revealed that only 2% of infants (at 23 weeks), 21% (at 24 weeks) and 69% (at 25 weeks) survived without severe abnormalities (Allen et al., New Eng. J. Med, 329: 1597-1601, 1993). White matter brain damage is a characteristic of these injuries. Patterns of damage range from subtle gliosis (telencephalic leukomalacia) through to severe cystic infarctions of the periventricular and subcortical white matter (Volpe, Prev. Med., 23: 638-645, 1994).
Histopathologic studies indicate some of these lesions develop prenatally, others postnatally. Poor neurological outcome is associated with the presence of these white matter injuries (Guit et al., Radiology, 175: 107-109, 1990). The severe periventricular lesions are strongly associated with cerebral palsy (Hoon, J. Perinatol., 15: 389-394, 1995).
Long term neurological outcome appears to be similarly compromised. In a group of less than 32 week old premature infants at the age of 9 years 19% were in special education, 32% were in a grade below the appropriate level for their age and 38% required special assistance (Hille et al., J Pediatr., 125: 426-434, 1994).
Similarly, another study has shown that in very premature infants about 5-15% develop major spastic motor deficits and an additional 25-50% exhibit developmental and cognitive disabilities (J. J. Volpe. Brain injury in the premature infantxe2x80x94Current concepts of pathogenesis and prevention. Biol Neonate 62:231-242, 1992).
The aetiology of these lesions is not completely understood (Armstrong, Semin. Perinatol., 17: 342-350, 1993), but are thought to occur secondary to various prenatal environmental and genetic factors (Lou, Brain Dev., 16: 423-431, 1994).
Cerebral hypoperfusion is considered to be a significant final common pathway in the pathogenesis of these encephalopathies (Lou, Brain Dev., 16: 423-431, 1994). Experimental and epidemiological studies generally support this hypothesis. For example, intrapartum acidosis and asphyxia in the premature infant carry a high risk of periventricular leukomalacia (Low et al., Am. J. Obstet. Gynaecol., 162: 977-981, 1990). Also, both increased levels of hypoxanthine and prolonged metabolic acidosis in the neonatal period are associated with a high risk of periventricular lesions (Russel et al., Arch. Dis. Child., 67: 388-392, 1992; Low et al., Am. J. Obstet. Gynaecol., 162: 977-981, 1990). In particular, periventricular lesions are probably caused by cerebral hypoxia-ischaemia following arterial hypotension (Iida et al., Pediatr. Neurol., 8: 205-209, 1992). Cerebral hypoxia-ischaemia may arise from problems associated with prematurity including respiratory distress syndrome, patent ductus arteriosis, necrotizing enterocolitis and sepsis. There is considerable variation in the pattern of lesions observed and a range of factors are likely to influence outcome, including gestational age and the severity and nature of the insult (Gluckman et al., Proceedings of The Alfred Benzon Symposium no. 37, Munksgaard, Copenhagen, 1993). Other factors such as hypoglycaemia, infections or toxaemia are also likely to be important (Piekkala et al., Early Hum. Dev., 13: 249-268, 1986).
Current methods for assessing brain injury reveal damaged areas of the brain, but do not identify those premature infants at risk of suffering a neural injury. Brain damage assessed by neurological examination is of limited prognostic value, especially for those preterm infants on life support. Ultrasonography is also used and reveals lesions as white matter echodensities and echoluciencies, which are useful in predicting future handicap, such as cerebral palsy. However, this approach is less suitable for monitoring and detecting pathophysiologic events which may occur over several days, the knowledge of which could be used to minimise or avoid further injury.
Greater reliance needs to be placed on other investigations such as pathophysiologic measures (Hill, Clin. Invest. Med., 16: 141-148, 1993). Doppler cerebral haemodynamic measures have not been proven to be predictive of outcome (Shortland et al., J. Perinat. Med., 18: 411-417, 1990). In the more mature brain the EEG signal can be used to predict severe loss of the superficial neurons that generate this signal (Williams et al Ann Neurol, 31:14-21 1992).
Two patterns of white matter damage can occur: xe2x80x98subtlexe2x80x99 white matter damage which manifests as gliosis, impaired myelination, ventriculomegaly and is often termed telencephalic leucomalacia; xe2x80x98severexe2x80x99 cystic infarctions within the perventricular and subcortical white matter. The former are associated with cognitive deficits and the latter lesions are strongly associated with cerebral palsy.
Histopathological studies indicate the timing of injury is variablexe2x80x94some may develop prenatally whereas many others appear to develop during the first postnatal weeks. However in surviving infants the timing of injuries is typically unclear and there are considerable problems with detecting when these white matter injuries occur (D. J. Murphy, M. V. Squier, P. L. Hope, S. Sellers and A. Johnson. Clinical associations and time of onset of cerebral white matter damage in very preterm babies. Arch Dis Child Fetal Neonat Ed 75 (1 Special Issue SI):F 27-F 32, 1996). The inability to detect the onset of injury makes management difficult. For example, if a subtle or severe injury to the deep white matter could be rapidly detected, then the injurious factor could be corrected or treatment applied.
The invention provides a method and system for detecting white matter neural injury and predicting neurological outcome particularly in preterm infants.
In broad terms in one aspect the invention comprises a method for detecting white matter neural injury and predicting neurological outcome for a patient, comprising:
acquiring EEG signal(s) from the surface of the head of the patient, and
analysing the frequency distribution of the signal(s) to produce output information indicative of cerebral white matter injury for the patient.
Preferably the method includes comparing the analysed data with stored comparative spectral edge and neurological outcome information to produce information useful for managing the patient.
In broad terms in another aspect the invention comprises a system for detecting neural injury and predicting neurological outcome for a patient, comprising:
means for acquiring EEG signal(s) from the surface of the head of a patient, and
computing means arranged to analyse the frequency distribution of the EEG signals to produce output information indicative of cerebral white matter injury for the patient.
An electroencephalogram or EEG provides a record of electrical activity from the most superficial layers of the cerebral cortex recorded from electrodes on the scalp. This activity is the result of the rhythmic discharging of neurons under the electrode. The EEG signal provides information about the frequency and amplitude of the neuronal electrical activity and its temporal variation. We have found experimentally that loss of spectral edge frequency is highly predictive of deep white matter damage in the preterm foetus. By preterm or premature is meant infants born at less than 37 weeks gestation. The method and system of the invention also have application in detecting white matter neural injury in child and adult patients however.